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Evaluating associations between vaccine response and malnutrition, gut function, and enteric infections in the MAL-ED cohort study: methods and challenges.

ABSTRACT: Most vaccine assessments have occurred in well-nourished populations of higher socioeconomic status. However, vaccines are often used in populations with high incidences of malnutrition and infections, in whom the effectiveness of some vaccines is inferior for unknown reasons. The degree and extent of vaccine underperformance have not been systematically studied for most vaccines across differing epidemiologic settings. This paper outlines the methods used and challenges associated with measuring immunological responses to oral vaccines against poliovirus and rotavirus, and parenteral vaccines against pertussis, tetanus, and measles in an observational study that monitored daily illness, monthly growth, intestinal inflammation and permeability, pathogen burden, dietary intake, and micronutrient status in children in 8 countries. This evaluation of vaccine response in the context of low- and middle-income countries is intended to address the gaps in knowledge of the heterogeneity in vaccine response in diverse epidemiological settings and the interplay between infections, nutrition, and immune response.

SUBMITTER: Hoest C

PROVIDER: S-EPMC4204607 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Evaluating associations between vaccine response and malnutrition, gut function, and enteric infections in the MAL-ED cohort study: methods and challenges.

Hoest Christel C Seidman Jessica C JC Pan William W Ambikapathi Ramya R Kang Gagandeep G Kosek Margaret M Knobler Stacey S Mason Carl J CJ Miller Mark M

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20141101

Most vaccine assessments have occurred in well-nourished populations of higher socioeconomic status. However, vaccines are often used in populations with high incidences of malnutrition and infections, in whom the effectiveness of some vaccines is inferior for unknown reasons. The degree and extent of vaccine underperformance have not been systematically studied for most vaccines across differing epidemiologic settings. This paper outlines the methods used and challenges associated with measurin ...[more]

PMID: 25305297

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Project description:BackgroundOpen drains are common methods of transporting solid waste and excreta in low-income urban neighborhoods. Open drains can overflow due to blockages with solid waste and during rainfall, posing exposure risks. The goal of this study was to evaluate whether pediatric enteric infection was associated with open drains and flooding in a dense, low-income, urban neighborhood.MethodsAs part of the MAL-ED study in Vellore, India, a cohort of 230 children provided stool specimens at 14-17 scheduled home visits and during diarrheal episodes in the first two years of life. All specimens were analyzed for enteric pathogens. Caregivers in 100 households reported on flooding of drains and households and monthly frequency of contact with open drains and flood water. Household GPS points were collected. Monthly rainfall totals for the Vellore district were collected from the Indian Meteorological Department. Clustering of reported drain and house flooding were identified by Kulldorff's Bernoulli Spatial Scan. Differences in enteric infection were assessed for household responses and spatial clusters, with interactions between reported flooding and rainfall to approximate monthly drain flooding retrospectively, using multivariable, mixed-effects logistic regression models.ResultsCoverage of household toilets was low (33%), and most toilets (82%) discharged directly into open drains, suggesting poor neighborhood fecal sludge management. Odds of enteric infection increased significantly with total monthly rainfall for children who lived in households that reported that the nearby drain flooded (4% increase per cm of rain: OR: 1.04, 95% CI: 1.00-1.08) and for children in households in a downstream spatial cluster of reported drain flooding (5% increase per cm of rain: OR: 1.05, 95% CI: 1.01-1.09). There was no association between odds of enteric infection and frequency of reported contact with drain or floodwater.ConclusionsChildren in areas susceptible to open drain flooding had increased odds of enteric infection as rainfall increased. Results suggested that infection increased with rainfall due to neighborhood infrastructure (including poor fecal sludge management) and not frequency of contact. Thus, these exposures may not be mitigated by changes in personal behaviors alone. These results underscore the importance of improving the neighborhood environment to improve children's health in low-income, urban settings.

Project description:BackgroundStunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites.MethodsWe administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites.ResultsAverage age of study children was 41 months. Mean food access insecurity score (range: 0-27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17).ConclusionsOur study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition.

Project description:BackgroundBreastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized.ObjectiveThe aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection.MethodsA total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen.ResultsInfants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo.ConclusionsIn this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

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Evaluating associations between vaccine response and malnutrition, gut function, and enteric infections in the MAL-ED cohort study: methods and challenges.

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Evaluating associations between vaccine response and malnutrition, gut function, and enteric infections in the MAL-ED cohort study: methods and challenges.

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